Avastin (and related drugs)
Avastin (also known as Bevacizumab) is a monoclonal antibody that is the first drug
explicitly designed to inhibit the growth of new blood vessels to receive FDA approval.
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It now is used for several different kinds of cancer, almost always in combination with
one or another form of chemotherapy. Its first use with brain tumors was reported at a
2005 European neuro-oncology conference. (62). Avastin at a dose of 5 mg/kg was given
every two weeks to 29 patients with recurrent tumors (apparently including both
glioblastomas and grade III tumors), following by weekly infusions thereafter. Patients
also received CPT-11 (irinotecan) concurrently with Avastin. Tumor regressions were
evident after the first course of treatment, with 19 patients having either complete or
partial regressions. Long-term survival data were not mature at the time of the report. It
remains to be seen whether Avastin will have comparable effects in combination with
chemotherapy drugs other than CPT-11. Avastin does increase the risk of intracranial
bleeding, but in the aforementioned clinical trial, this occurred for only 1 of the 29
patients. A second study from a different research group (63) reported tumor regressions
in 4 of 10 GBM patients and in 3 of 4 grade III gliomas. Even more impressive results
have come from a third study, involving 32 patients (23 GBM), in which there were 19
partial regressions and one complete regression (64). The high percentage of tumor
regressions stands in contrast to the typical response rate to other treatments for recurrent
GBM, which is 5-10%. This protocol thus appears among the most promising available,
with the biggest issue regarding its use being the duration of its benefit.
A second new drug targeting angiogenesis, only recently approved by the FDA, is Sutent
(made by Pfizer, generic name is sunitinib). Unlike Avastin which is given intravenously,
Sutent is taken orally. Also, whereas Avastin targets only one of the signaling channels
(VEGF) that stimulate angiogenesis, Sutent targets multiple signals. .Sutent has not yet
been tested with gliomas, although it has FDA approval for both renal cell cancer and
gastro-intestinal stromal tumors, indicating that it likely to have broad applicability. Yet a
third drug that targets angiogenesis, which received recent FDA approval is Nexaver
(made by Bayer, generic name is sorafenib), which like Sutent targets multiple signaling
pathways but has not yet been tested with gliomas.